FDA Approves Darolutamide for Metastatic Hormone-Sensitive Prostate Cancer

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On August 5, 2022, the U.S. Food and Drug Administration approved darolutamide (Nubeqa) tablets in combination with docetaxel for adult patients with metastatic hormone-sensitive prostate cancer. The evaluation of efficacy was based on ARASENS ( identifier NCT02799602), a randomized, multicenter, double-blind, placebo-controlled clinical trial in 1,306 patients with the disease.


Patients in ARASENS were randomly assigned to receive either darolutamide at 600 mg orally twice daily plus docetaxel at 75 mg/m2 intravenously administered every 3 weeks for up to six cycles or docetaxel plus placebo. All patients received a gonadotropin-releasing hormone analog concurrently or had a bilateral orchiectomy.

The primary efficacy measure was overall survival. Time to pain progression was an additional efficacy measure. Median overall survival was not in the darolutamide plus docetaxel arm and 48.9 months (95% confidence interval [CI] = 44.4 months to not reached) in the docetaxel-plus-placebo arm (hazard ratio [HR] = 0.68, 95% CI = 0.57–0.80; P < .0001). Treatment with darolutamide and docetaxel resulted in a statistically significant delay in time to pain progression (HR = 0.79, 95% CI = 0.66–0.95; 1-sided P = .006).

The median age of patients was 67 years (range = 41–89), and 17% were aged 75 years or older. Selected demographics were reported as follows: 52% White, 36% Asian, 4% Black or African American, 7% Hispanic/Latino. Approximately 3% of patients had M1a disease (spread to distant lymph nodes), 83% had M1b (spread to bones), and 14% had M1c (spread to organs).

The most common adverse reactions experienced by patients (incidence ≥ 10% with a ≥ 2% increase over placebo with docetaxel) were constipation, decreased appetite, rash, hemorrhage, increased weight, and hypertension. The most common laboratory test abnormalities (≥ 30%) were anemia, hyperglycemia, decreased lymphocyte count, decreased neutrophil count, increased aspartate transaminase, increased alanine transaminase, and hypocalcemia.

More About the Approval

The recommended darolutamide dose for metastatic hormone-sensitive prostate cancer is 600 mg (two 300-mg tablets) taken orally, twice daily, with food until unacceptable toxicity or disease progression. Docetaxel, 75 mg/m2 intravenously, is administered every 3 weeks for up to six cycles. The first dose of docetaxel should be administered within 6 weeks after the start of darolutamide treatment.

This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. For this review, the FDA collaborated with Health Canada, the Singapore Health Sciences Authority, Switzerland’s Swissmedic, the United Kingdom’s Medicines and Healthcare products Regulatory Authority, and Australia’s Therapeutic Goods Administration. The application reviews may be ongoing at the other regulatory agencies.

This review used the Real-Time Oncology Review pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application approximately 1 month ahead of the FDA goal date. This application was also granted Priority Review.